Racemization of atropisomeric bis(phosphine oxide) compounds

ABSTRACT

A process for the racemization of atropisomeric bis(phosphine oxide) compounds of formula I:                    
     in their (S) or (R) or non-racemic form, is useful for preparing optical active bisphosphine ligands, that form optical active complexes with transition metals. Racemization is thermal and carried out in high or low boiling solvent, under normal or elevated pressure at 10 5  to 3.5×10 7  Pa. Heating is performed in a system that allows heating up to 400° C. (reactor, autoclave, aluminum block, round-bottom flask with heating/stirring mantle and the like) or by microwave irradiation or in the melt at a temperature from 260 to 400° C.

SUMMARY OF THE INVENTION

The subject invention provides a process for the racemization of acompound of the formula:

which is present in the (R) form, the (S) form, or a non-racemic mixtureof the (R) form and (S) form. In the compound of formula I, R¹isC₁₋₈-alkoxy and R² is hydrogen, C₁₋₈-alkyl, or C₁₋₈-alkoxy.Alternatively, R¹ and R² taken together are methylenedioxy orethylenedioxy. R³ is hydrogen, C₁₋₈-alkyl, or C₁₋₈-alkoxy. R⁴ is phenylor phenyl monosubstituted in the meta- or para-position by C₁₋₈-alkyl,C₁₋₈-alkoxy, di- C₁₋₈-alkylamino, trialkylsilyl or phenyl. This processcomprises heating the compound of formula I to a temperature of fromabout 260° C. to about 400° C. for a time sufficient to causeracemization of the compound of formula I.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The subject invention will now be described in terms of its preferredembodiments. These embodiments are set forth to aid in understanding theinvention but are not limiting.

The present invention is concerned with a novel process for theracemization of atropisomeric compounds of formula I,

The optical active compounds of formula I above are known, as are theintermediates for the preparation of optically active bisphosphineligands of formula II,

which form optically active complexes with transition metals. Thesecomplexes are used as catalysts in a number of asymmetric reactions.

Synthesis of optically active intermediates of formula I and ligands offormula II by known processes typically use a racemic mixture (mixtureof equal amounts of both enantiomers) of the product, that is resolvedfor the preparation of the optical active ligands of formula II, whichare in turn used for the preparation of catalysts. The synthesis ofoptically active bisphosphine ligands of formula II thus involves theformation of a racemic mixture of the bis(phosphine oxide) of formula I,subsequent racemic resolution and reduction to obtain the desiredenantiomer or reduction to the racemic bisphosphine of formula IIfollowed by racemic resolution. The present invention provides a methodto use the undesired enantiomer of the intermediate of formula I inorder to improve the efficiency of the synthesis of optical activeligands of formula II.

The present invention is thus concerned with a novel process for theracemization of atropisomeric compounds of formula I,

which are present in the (R) or (S) form or a non-racemic mixture of the(R) and (S) form and wherein

R¹ signifies C₁₋₈-alkoxy and

R² signifies hydrogen, C₁₋₈-alkyl, C₁₋₈-alkoxy or

R¹ and R² together signify methylenedioxy or ethylenedioxy

R³ signifies hydrogen, C₁₋₈-alkyl or C₁₋₈-alkoxy and

R⁴ signifies phenyl or substituted phenyl,

characterized in that the racemization is thermal and carried out at atemperature from 260 to 400° C., preferably from 280 to 380° C.

The term “racemization” signifies the transition of an optical activecompound towards the corresponding racemate. A racemate signifies amixture of equal amounts of both enantiomers. It is to be understoodthat racemization need not be complete to be within the scope of theinvention. Thus, the transformation of a (R) to (S) mixture that is inthe ratio of 10 to 1 via the subject process into a more racemic mixtureof 6 to 4 would be considered within the scope of the invention.

The term “atropisomeric” indicates the stereochemistry of compounds inwhich the free rotation along a bond is hindered and optical activityresults. Atropisomerism is a special case of axial chirality.

The term “C₁₋₈-alkyl” signifies in the scope of the present inventionhydrocarbons with 1 to 8 carbon atoms, i.e. straight-chain or branchedalkyl groups such as, for example, methyl, ethyl, propyl, isopropyl,butyl, isobutyl, tert.-butyl, pentyl, isopentyl, neopentyl, hexyl,isohexyl, tert.-hexyl, heptyl, and octyl.

The term “C₁₋₈-alkoxy” signifies a C₁₋₈-alkyl group as defined abovewhich is bonded via an oxygen atom. Methoxy, ethoxy, propoxy,isopropoxy, butoxy, and the like can be mentioned as example.

The term “substituted phenyl” signifies in the scope of the presentinvention phenyl groups which are monosubstituted in the meta- orpara-position, preferably in the para-position. Suitable substituentsfor the phenyl group are C₁₋₈-alkyl, preferably methyl; or C₁₋₈-alkoxy,preferably methoxy; or di-C₁₋₈-alkylamino, preferably dimetylamino; ortrialkylsilyl, preferably trimethylsilyl; or substituted by a phenylgroup.

According to the invention, the racemization of the compounds of theformula I is carried out by heating the compound in a solvent or in themelt at a temperature from 260 to 400° C. The “melt” means a liquidresulting from the heating of a compound of formula I. The heating iscarried out in a device which allows for heating up to 400° C. For smallscale the heating can be carried out e.g. with a heating/stirringmantel, an aluminum heating block, an electrically heated reactor orautoclave and the like or by microwave irradiation. For larger scale theheating can be carried out e.g. in reactors or autoclaves. The reactionis carried out batchwise or in a continuous manner.

In a preferred way, the racemization of the compounds of the formula Iis carried out in a high boiling solvent at a temperature from 260 to400° C. batchwise or in a continuous manner and optionally underpressure at 10⁵ to 3.5×10⁷ Pa or preferably at 10⁵ to 10⁷ Pa. Suitablehigh boiling solvents are compounds of formula

R⁵O(CH₂CH₂O)_(n)CH₂CH₂OR⁶  III

wherein R⁵ and R⁶ each independently signify hydrogen or lower alkyl(C₁-C₄), and

n is 2,3,4,5,6,7 or higher to signify a polyethylenoxy chain.

Examples of solvents of formula III are tetraethylene glycol,tetraethylene glycol dimethyl ether, polyethylene glycol monomethylether 350, polyethylene glycol dimethyl ether 400 or polyethylene glycol350, polyethylene glycol 400, polyethylene glycol 550 and polyethyleneglycol 725.

Further suitable high boiling solvents are solvents of formula

R⁵O(CH₂CH(CH₃)O)_(n)CH₂CH(CH₃)OR⁶  IV

wherein R⁵ and R⁶ are as mentioned above, and

wherein n is as mentioned above to signify a polypropylenoxy chain.

A preferred solvent of formula IV is polypropylene glycol 725.

A further preferred solvent is polyoxyethylen-sorbitan-monooleat. Thereaction can also be carried out in inorganic salt melts.

In another preferred aspect of the invention the racemization of thecompounds of the formula I is carried out in a low boiling organicsolvent under pressure at 10⁵ to 3.5×10⁷ Pa, preferably at 10⁵ to 10⁷Pa. Suitable solvents are aromatic solvents like benzene, toluene,xylene, or alcohols like methanol, ethanol, propanol, butanol, or amixture of the mentioned solvents. Preferred solvents are toluene,ethanol or a mixture of both solvents.

According to the invention the racemization is carried out batchwisei.e. by a reaction in which the reactant is added to a reaction system(e.g. round flask) once and after the reaction the product is separated.In the alternative, according to the invention, the racemization iscarried out in a continuous manner i.e. by a continuous running reactionin which the reactant is continuously added to a reaction system (e.g.reactor) and the product is continuously separated.

In a further preferred embodiment, the racemization is carried out inthe melt at a temperature from 260 to 400° C. under normal or elevatedpressure at 10⁵ to 3×10⁵ Pa or in a preferred way at a temperature from280 to 380° C. and the same pressure.

In a preferred embodiment a specific amount of the optical active ornon-racemic mixture of the intermediate of formula I is heated in a highor low boiling solvent or in the melt form under argon or undernitrogen. The heating is carried out in a device which allows forheating up to 400° C. For small scale the heating can be carried oute.g. with a heating/stirring mantel, an aluminum heating block, anelectrically heated reactor or autoclave and the like or by microwaveirradiation. For larger scale the heating can be carried out e.g. inreactors or autoclaves. When a low boiling solvent is used the compoundof formula I is heated in an autoclave under elevated pressure at 10⁵ to3.5×10⁷ Pa. The reaction is carried out batchwise or in a continuousmanner. After the reaction, a racemic resolution is carried out and thenthe (R) or (S) form of the bis(phosphine oxide) of formula I is reducedto the (R) or (S) form of bisphosphine ligands of formula II. Or in analternative, after the racemization, a reduction of the racemic mixtureof compound of formula I to ligands of formula II is carried out andthen a racemic resolution is carried out to the (R) or (S) form of thebisphosphine ligands of formula II.

The invention is further concerned with the use of the inventive processfor the preparation of atropisomeric ligands of the formula II in thepure (R) or (S) form

wherein the symbols are defined as above, characterized in that

a) the racemic mixture of bis(phosphine oxides) of formula I is resolvedand

b) the (R) or (S) form of the bis(phosphine oxide) of formula I isreduced to the (R) or (S) form of the bisphosphine ligand of formula IIor

a) the racemic mixture of bis(phosphine oxides) of formula I is reducedto form a racemic mixture of bisphosphine ligands of formula II and

b) a racemic resolution of the racemic mixture of ligands of formula IIis carried out to obtain the (R) or (S) form of the bisphosphine ligandof formula II.

The preparation of compounds of formula I is known and described forexample in U.S. Pat. No. 5,274,125.

Both, the racemic resolution and the reduction of compounds of formula Ito compounds of formula II are known and described for example inHelvetica Chimica Acta Vol. 74 (1991) p.370 et seq.

In a typical reaction, the thermal racemization is carried out with acompound of formula I in which R¹ signifies methoxy, R² and R³ signifyhydrogen, and R⁴ signifies phenyl ((R) or (S)-MeOBIPHEPO) in a highboiling solvent or in the melt at a temperature from 260 to 400° C.under normal or elevated pressure at 10⁵ to 3.5×10⁷ Pa or in a lowboiling organic solvent at the same temperature under elevated pressureat 10⁵ to 3.5×10⁷ Pa.

Compounds of formula I are valuable intermediates in the production ofbiphosphine ligands of formula II, which are used for the formation ofcomplexes with transition metals, especially with transition metals ofGroup VIII, such as, for example, ruthenium, rhodium or iridium. Thesecomplexes are useful as catalysts in asymmetric reactions such asasymmetric hydrogenations. Complexes of diphosphine ligands withtransition metals as well as their use for asymmetric reactions such asasymmetric hydrogenations are known and are described, for example, inU.S. Pat. No. 5,430,191.

The following examples illustrate the invention and in no mannerrepresent a limitation thereof. In these examples the abbreviations usedhave the following significances:

HPLC high performance liquid chromatography NMR nuclear magneticresonance spectroscopy rt room temperature HV high vacuum e.e.enantiomeric excess TLC thin layer chromatography min minute(s) hrhour(s) MeOBIPHEPO (6,6′-dimethoxybiphenyl-2,2′-diyl)bis(diphenyl-phosphine oxide) DiMeOBIPHEPO(5,5′,6,6′-tetramethoxybiphenyl-2,2′-diyl)bis(di- phenylphosphine oxide)pTol-MeOBIPHEPO (6,6′-dimethoxybiphenyl-2,2′-diyl)bis(di-p-tolyl-phosphine oxide) PEG 400 polyethylene glycol 400 Tween 80polyoxyethylen-sorbitan-monooleat

All temperatures are given in degrees Celsius.

EXAMPLE 1

Racemization of (S)-MeOBIPHEPO in polyethylene glycol.

1.1) A 100 ml 2-neck round bottom flask equipped with stirring bar anddistillation bridge was charged under argon with 10.0 g (16.28 mmol) of(S)-MeOBIPHEPO [99.2% ee; HPLC-purity: 99.6%] and 50 ml of polyethyleneglycol. The mixture was heated for 2 hr. The internal reactiontemperature rose from rt to 317° C. within 1 hr. The resulting solutionwas further stirred for 1 hr whereby the temperature rose to 344° C. andca. 5 ml of a yellow liquid was collected by distillation. The reactionmixture was cooled to rt, 100 ml of dichloromethane were added and thesolution was washed with water (3×40 ml). The organic phase was driedover MgSO₄, filtered and the filtrate concentrated to ca. 50 ml. Then,50 ml of methanol was added and the mixture was concentrated to a volumeof ca. 30 ml. This procedure was repeated two more times. The resultingsuspension was kept overnight in the refrigerator, the crystals werefiltered, washed with cold methanol (2×10 ml) and dried to afford 9.64 gof (RS)-(MeOBIPHEPO) as an off-white solid, HPLC-purity: 96.4%; m.p.310-312° C. According to an HPLC-analysis on a chiral column (chiralHPLC) this material consisted of a mixture of 50.4% (S)-(MeOBIPHEPO) and49.6% (R)-(MeOBIPHEPO). [α]²⁰D=−0.09(c=1.12, CHCl₃).

In an analogous experiment, 10 g of (S)-(MeOBIPHEPO) was treated at amaximum temperature of 337° C. for 2.5 hr to afford 9.56 g of(RS)-(MeOBIPHEPO); HPLC-purity: 95.6%; chiral HPLC: 50.5%(S)-(MeOBIPHEPO) and 49.5% (R)-(MeOBIPHEPO).

EXAMPLE 1.2-1.8

In the following examples (S)-MeOBIPHEPO was racemized in the followinghigh boiling solvents: tetraethylene glycol, tetraethylene glycoldimethyl ether, polyethylene glycols 350, 400 and 550, respectively,polypropylene glycol 725 and Tween 80. The results are compiled inTable 1. In all examples a suspension of 150 mg (0.24 mmol) of(S)-MeOBIPHEPO in 2.0 ml of the solvent was heated in a glass tube in analuminum heating block at 330° C. for 70 min or 350° C. for 40 min.After cooling to rt, the reaction mixture was worked-up and analyzed byHPLC.

TABLE 1 Racemization of (S)-MeOBIPHEPO in different solvents ex- am- T tHPLC^(b)) ple solvent [° C.] [min] work-up^(a)) % (S) % (R) 1.2tetraethylene glycol 350 40 1 61 39 1.3 tetraethylene glycol 350 40 2 7228 dimethyl ether 1.4 polyethylene glycol 350 40 3 65 35 monomethylether 350 1.5 polyethylene glycol 350 40 3 60 40 dimethyl ether 400 1.6polyethylene glycol 330 70 1 56 44 550 1.7 polypropylene 330 70 1 53 47glycol 725 1.8 Tween 80 330 70 1 54 46 ^(a))Procedure 1: Dissolved inCH₂Cl₂, washed with H₂O, dried over Na₂SO₄, filtered and evaporated.Procedure 2: Precipitated by addition of hexane and then collected byfiltration. Procedure 3: Precipitated by addition of hexane/toluene. Theprecipitate was collected by filtration, washed with 3 portions ofhexane and dried. ^(b))HPLC-analysis on a chiral column.

EXAMPLE 2

Continuous racemization of (R)-MeOBIPHEPO in ethanol.

100 g of (R)-MeOBIPHEPO was dissolved under argon in 1500 ml of ethanoland pumped through a preheater at 200° C. and then through a heated pipereactor at 350° C. The residence time in the pipe reactor was 15.6 minat a flow rate of 8 ml/min, the pressure increased to 3×10⁶ Pa. Thereaction solution was cooled to rt. Filtration of the crystallineprecipitate afforded 63.21 g of a white powder; HPLC-purity 94.7%(RS)-MeOBIPHEPO; chiral HPLC 50:50 mixture of (R)-MeOBIPHEPO and(S)-MeOBIPHEPO; calculated yield 60%. From the mother liquor anadditional of 29.75 g of solid material was isolated; HPLC-purity 60.4%(RS)-MeOBIPHEPO; chiral HPLC 50:50 mixture of (R)-MeOBIPHEPO and(S)-MeOBIPHEPO; calculated yield 18%; total yield 78%.

In an analogous experiment the reaction was accomplished with aresidence time in the pipe reactor of 10.2 min at a flow rate of 12.2ml/min. The result was the same as described above.

EXAMPLE 3

Batch racemization of (R)-MeOBIPHEPO in ethanol.

3.1) An autoclave was charged with 1.0 g of (R)-MeOBIPHEPO and 12.5 mlof ethanol, closed and flushed with argon. After heating up to 350° C.in a metal bath, the pressure increased to 1.37×10⁷ Pa. After 30 min thereaction was stopped. The brown solution was evaporated under reducedpressure (52° C./5.1×10³ Pa) to afford 1.0 g of a brown residue of(RS)-MeOBIPHEPO; HPLC purity 84%; chiral HPLC 53.5% (R)-MeOBIPHEPO and46.5% (S)-MeOBIPHEPO.

Further racemizations of (R)-MeOBIPHEPO under pressure were carried outin various solvents as described in example 3.2-3.8. The results arecompiled in Table 2.

TABLE 2 Racemization of 1.0 g (R)-MeOBIPHEPO under pressure in differentsolvents p crude temp [Pa] time material example solvent [ml] [° C.]×10⁵ [min] [g]^(a)) % (R)^(b)) % (S)^(b)) 3.1 EtOH [12.5] 350 137 351.00 53.5 46.5 3.2 PEG400 330 — 90 2.18 — — [5.0] 3.3 Tol/EtOH 350 78 351.00 52.9 47.1 7:3 [12.5] 3.4 PEG 400 350 1 35 2.28 52.8 47.2 [5.0] 3.5EtOH [12.5] 350 128 35 1.02 50.5 49.5 3.6 Tol/EtOH 350 68 35 0.99 51.548.5 7:3 [12.5] 3.7 EtOH [12.5] 350 138 50 0.97 49.7 50.3 3.8 EtOH[12.5] 350 135 20 0.93 53.5 46.5 ^(a))Crude material obtained afterevaporation or after aqueous work-up (examples 3.2 and 3.4),respectively. ^(b))By HPLC-analysis on a chiral column.

EXAMPLE 4

Racemization of (S)-MeOBIPHEPO in the melt.

4.1) Ten test tubes were charged with 1.0 g each of (S)-MeOBIPHEPO, fora total of 10.0 g (16.3 mmol). The test tubes were heated in thealuminum block at 350° C. for 20 min. After cooling, the oily, browncontent of the test tubes was transferred into a round bottom flaskusing ca. 200 ml of methylene chloride and 200 ml of methanol. Thesolution was concentrated to a volume of ca. 50 ml and 200 ml ofmethanol was added. After concentration to ca. 50 ml, the resultingsuspension was kept overnight in the refrigerator. The crystals werecollected by filtration, washed with cold methanol and dried to afford8.9 g of (RS)-MeOBIPHEPO as off-white powder; HPLC purity 97%; chiralHPLC 51% (S)-MeOBIPHEPO and 49% (R)-MeOBIPHEPO; calculated yield: 86%.

4.2) An autoclave with stirring bar was charged with 50.0 g of(R)-MeOBIPHEPO, closed and flushed with argon. The reaction was heatedto 350° C. The heating was stopped after 45 min. After cooling to rt,the light yellow solid compound obtained was dissolved in 150 ml ofCH₂Cl₂, the solution transferred into a round bottom flask andevaporated under reduced pressure (50° C./4×10³ Pa). The solid residuewas dissolved in 150 ml of MeOH (70° C., reflux) and crystallized in therefrigerator at 4° C. overnight. The crystals were collected byfiltration, washed with cold methanol (50 ml) and dried (70° C./6.5×10³Pa) to afford 42.56 g (yield: 85.1%) of (RS)-MeOBIPHEPO as off-whitepowder; chiral HPLC 49.9% (S)-MeOBIPHEPO and 50.1% (R)-MeOBIPHEPO.

EXAMPLES 5-8

TABLE 3 Racemization of MeOBIPHEPO analogues were carried out in themelt or in tetraethylene glycol as solvent. ex- HPLC^(b)) am- conc.^(a))reaction % % ple analogue % ° C. min (S) (R) remarks 5 (S)- 2.2 330 4070.2 29.8 c) DiMeOBIPHEPO 6 (R)- 2.1 330 240 50.3 49.7 c) DiMeOBIPHEPO 7(S)-pTol- 7.5 330 60 59.7 40.3 c) MeOBIPHEPO 8 (S)-pTol- melt 330 6076.5 23.5 d,e) MeOBIPHEPO ^(a))Concentration of the MeOBIPHEPO analoguein tetraethylene glycol. ^(b))HPLC analysis on a chiral column. c)Experimental procedure as described in example 1. d) Experimentalprocedure as described in example 4. e) Some decomposition according toTLC analysis.

EXAMPLE 9

Racemization of (S)-MeOBIPHEPO in an organic solvent under microwaveirradiation

A reactor tube of 40×260 mm fitted with a mechanical stirrer, a refluxcondenser and an argon inlet tube was charged with 10.0 g (16.3 mmol)of(S)-MeOBIPHEPO and 50 ml of polyethylene glycol 400. The reactor tubewas placed in a microwave reactor. The suspension was stirred undermicrowave irradiation. The internal reaction temperature rose from rt to280° C. within 6 min. This temperature was maintained for an additional64 min. The reactor tube was then removed and allowed to cool. Theresulting brown-black solution was analyzed by HPLC on a chiral columnand found to contain 52.4% of (S)-MeOBIPHEPO and 46.6% of(R)-MeOBIPHEPO. Work-up and crystallization from methanol afforded 8.9 g(89%) of (RS)-MeOBIPHEPO as an off-white solid; chiral HPLC 50.4%(S)-MeOBIPHEPO and 49.6% (R)-MeOBIPHEPO.

Upon reading the present specification, various alternative embodimentswill become obvious to the skilled artisan. These variations are to beconsidered within the scope and spirit of the invention, which is onlylimited by the claims that follow and their equivalents.

What is claimed is:
 1. A process for the racemization of a compound ofthe formula I:

which is present in the (R) form, the (S) form, or a non-racemic mixtureof the (R) form and (S) form, wherein R¹ is C₁₋₈-alkoxy, and R² ishydrogen, C₁₋₈-alkyl, or C¹⁻⁸-alkoxy, or R¹ and R² taken together aremethylenedioxy or ethylenedioxy; R³ is hydrogen, C₁₋₈-alkyl, orC₁₋₈-alkoxy; and R⁴ is phenyl or phenyl monosubstituted in the meta- orpara-position by, C₁₋₈-alkyl, C¹⁻⁸-alkoxy, di- C₁₋₈-alkylamino,trialkylsilyl or phenyl; which comprises heating the compound of formulaI to a temperature of from about 260° C. to about 400° C. for a timesufficient to cause racemization of the compound of formula I.
 2. Theprocess according to claim 1 wherein the racemization is carried out ina solvent or in a melt.
 3. The process according to claim 2 wherein theheating is by microwave irradiation.
 4. The process according to claim 2wherein the heating is in a solvent that has a boiling point above theheating temperature.
 5. The process according to claim 4 wherein theheating is in a solvent of formula: R⁵O(CH₂CH₂O)_(n)CH₂CH₂OR⁶  IIIwherein R⁵ and R⁶, each independently, are hydrogen or C₁-C₄-alkyl, andn is an integer greater than
 2. 6. The process according to claim 5wherein n is an integer of from 2 to
 7. 7. The process according toclaim 4 wherein heating is in a solvent of formula:R⁵O(CH₂CH(CH₃)O)_(n)CH₂CH(CH₃)OR⁶  IV wherein R⁵ and R⁶, eachindependently, are hydrogen or C₁-C₄-alkyl, and n is an integer greaterthan
 2. 8. The process according to claim 7 wherein n is an integer offrom 2 to
 7. 9. The process according to claim 2 wherein heating is in asolvent selected from the group consisting of tetraethylene glycol,tetraethylene glycol dimethyl ether, polyethylene glycol monomethylether 350, polyethylene glycol dimethyl ether 400, polyethylene glycol350, polyethylene glycol 400, polyethylene glycol 550, polyethyleneglycol 725, polypropylene glycol 725, andpolyoxyethylen-sorbitan-monooleat.
 10. The process according to claim 2wherein the heating is in a solvent and under a pressure of from about10⁵ Pa to about 3.5×10⁷ Pa, the solvent having a boiling point above theheating temperature at the pressure used.
 11. The process according toclaim 10 wherein the heating is in a solvent under a pressure of fromabout 10⁵ Pa to about 10⁷ Pa.
 12. The process according to claim 10wherein the solvent is an aromatic solvent, an alcohol, or a mixture ofan aromatic solvent and an alcohol.
 13. The process according to claim 1wherein the heating is at a temperature of from about 280° C. to about380° C.
 14. The process according to claim 1 wherein the compound offormula I is (6,6′-dimethoxybiphenyl-2,2′-diyl)bis(diphenylphosphineoxide).
 15. The process according to claim 1, wherein the compound offormula I is(5,5′,6,6′-tetramethoxybiphenyl-2,2′-diyl)bis(diphenylphosphine oxide).16. The process according to claim 1 wherein the compound of formula Iis (6,6′-dimethoxybiphenyl -2,2′-diyl)bis(di-p-tolylphosphine oxide).